Diabetes is a major and rapidly growing problem: there are estimates that over 170 million people suffer from the disorder worldwide. In addition, studies have shown that the incidence of juvenile-onset, insulin-dependent diabetes has doubled over the last 15 years. There has also been a doubling in the number of children under the age of 5 suffering from diabetes in just 10 years.
The symptoms associated with diabetes can be severe. If the blood glucose level is not suitably controlled by the patient, the physical damage which may be caused includes blindness, heart disease and gangrene. As such, the mortality rate for diabetics is significantly higher than the rate for the average person.
A person's blood glucose concentration varies over a relatively short timescale, due to a number of factors, such as the length of time since the patient's last meal, the type of food ingested, the amount of exercise taken, and whether or not the patient is otherwise ill. As a result, diabetics usually need to test their glucose levels many times a day, in order to monitor and control their condition. The actual testing regime varies between patients and is individually prescribed by the doctor or diabetes educator of the patient.
The primary method used for testing blood glucose concentration involves the taking of a blood sample, which is then analysed. In this test, a patient's finger or arm is pricked with a small needle and the resulting drop of blood is placed on a test strip, for analysis in a hand-held meter. If the glucose concentration reading is above an acceptable level, insulin must be injected into the blood stream to bring the glucose concentration back within an acceptable range.
Because of the frequency of testing required to monitor the blood glucose concentration, the patient is normally expected to perform the tests throughout the day, drawing and analysing the blood sample himself. There are a number of problems experienced by patients with the above procedure. Firstly, the technique is invasive and therefore carries the risk of infection. Secondly, continual pricking of the fingers causes hard skin. Thirdly, the process is clearly not pain-free. Finally, there is a large, ongoing consumables cost associated with this method. As a result of these and other problems, certain sectors of the diabetic population do not test themselves as often as required. This is particularly the case for the elderly, who tend to lack the fine motor skills required; teenagers, who tend to find the whole procedure socially embarrassing; and children, who tend not to accept the discomfort associated with the process.
A number of non-invasive blood glucose concentration measuring techniques have been proposed to overcome these problems. One particular approach which has been suggested involves measuring the glucose concentration of the aqueous humor in the anterior chamber of the eye, since, while varying between individuals, there is a close correlation between this concentration and the blood glucose concentration. Measurement of the glucose concentration of the aqueous humor may be achieved by various means; for example, by polarimetry (e.g., U.S. Pat. No. 5,896,198); by Raman techniques (e.g., WO-A-00/02479); by spectrometry (e.g., U.S. Pat. No. 5,969,815); or by reflectometry (e.g., U.S. Pat. No. 6,236,089).
A desirable alternative approach to measuring the glucose concentration in the aqueous humor involves measuring the refractive index of the aqueous humor, since there is a strong correlation between the refractive index and the glucose concentration.
U.S. Pat. No. 3,963,019 discloses a method and apparatus, by which a beam of light is projected into and through the aqueous humor of a patient's eye. The angular displacement of light reflected from the iris and through the aqueous humor is proportional to the refractive index of the aqueous humor. Hence by measuring the angle of the reflected light, the glucose concentration of the aqueous humor may be found. In practice, this technique measures the combined optical properties of the aqueous humor and the cornea and it is not trivial to deconvolve the effect of each. In addition, changes to the cornea, for example, will reduce the accuracy of readings taken in this way.
U.S. Pat. No. 6,152,875 discloses a method and apparatus, by which the refractive index of the aqueous humor may be derived by measuring the intensity of light reflected from the eye. The intensities of reflected light from the air/cornea and cornea/aqueous humor interfaces are measured and compared to determined how much light is reflected from the cornea/aqueous humor interface relative to the cornea/air interface. It is assumed that the amount of light reflected from the air/cornea interface is constant, and that the amount of light reflected from the cornea/aqueous humor interface is related to the refractive index of the aqueous humor. There are a number of practical limitations to this technique. For example, any stray light or reflections from other surfaces will cause inaccuracies in measurements, so additional steps such as interferometry, frequency shift, or ultra-short pulses are required to achieve the required accuracy. Since the method relies on the measurement of the relative reflected intensities from two surfaces of the eye, further inaccuracies may be introduced because of diurnal variations in the shape of the cornea, changes in the refractive index of the tear film (itself affected by the blood glucose level) and variations in atmospheric conditions, such as temperature and pressure, which will alter the refractive index of the air.
WO-A-03/025562 discloses an interferometric technique for measuring the refractive index of the aqueous humor. In this technique, two beams of light are shone onto the iris in the eye, one beam having a plane wavefront and the other beam having a spherical wavefront. The two beams interfere where they coincide on the iris, to form a pattern of dark and light rings at a detector. Changes in the refractive index of the aqueous humor affect the phase difference between the interfering beams and therefore the spacing of the fringes. The refractive index may thus be determined by measuring the spacing of the fringes. One practical problem with this technique is that a laser is required. A further problem is that interferometry is very sensitive to vibrations, with the result that the apparatus effectively needs to be arranged on an optical bench. In particular, this technique would not be suitable for use with a hand-held meter. Furthermore, with this interferometric arrangement, it is not possible to distinguish between corneal changes and changes in the aqueous humor.
There is a need, therefore, for an apparatus and method which employs a non-invasive, optical technique for the reliable determination of changes in the refractive index of the aqueous humor in the anterior chamber of an eye. In particular, it would be desirable for measurements made by such apparatus and method to be used to derive the concentration of glucose in the aqueous humor and, in turn, the concentration of glucose in the blood of a patient. There is also a need for an apparatus and method which may be used to determine the concentrations of other compounds in the aqueous humor, including both naturally occurring and intentionally introduced chemicals, and which may be used to measure other properties of the eye, such as corneal thickness and surface curvature.
The present invention aims to address the above and other objectives by providing an improved technique for the measurement of properties of an eye.